肺癌循环肿瘤细胞的研究进展

转移是导致肺癌患者死亡的主要因素,积极防治转移的发生是提高患者疗效的关键。循环肿瘤细胞（CTCs）是启动远处转移的重要环节,自原发灶脱落开始即触发一系列转移级联反应,最终在远处靶器官定植和增殖。近年来,肺癌CTCs的检测技术手段不断优化,不仅可以对CTCs进行计数,还可鉴定不同亚群。肺癌CTCs检测可用于早期筛查、手术及放化疗后的预后预测、免疫靶向治疗的疗效评价等方面,动态监测肿瘤异质性,有助于调整个体化治疗方案,达到精准治癌的目的。田建辉研究组建立世界首例人肺腺癌循环肿瘤细胞系,将其融入肺癌亚临床核心病机“正虚伏毒”学说的探索,并积极促进肺癌特异性研究平台的构建,以期提高肺癌转移的研究和防控效率。     

循环肿瘤细胞及其与肿瘤转移复发的相关性研究

肿瘤细胞血液播散至远处器官和后来形成的转移灶是上皮来源恶性肿瘤最主要的死亡原因。对恶性肿瘤发生远处转移和复发等研究认为是由外周血中存在的循环肿瘤细胞所致(circulating tumor cell,CTC)。CTCs存在于外周循环中,激发机体的免疫反应,大部分肿瘤细胞被机体免疫系统所识别难以生存,只有小部分细胞继续在循环中,穿透基底膜,侵出血管在远端形成肿瘤转移灶。CTCs是肿瘤发生远处转移的必要条件,深入研究循环肿瘤细胞有助于对肿瘤的转移机制有更多的了解。本文对CTCs的分离与鉴定技术方法和CTCs与肿瘤复发转移的机制进行综述。     

循环肿瘤细胞及其与肿瘤转移复发的相关性研究

肿瘤细胞血液播散至远处器官和后来形成的转移灶是上皮来源恶性肿瘤最主要的死亡原因。对恶性肿瘤发生远处转移和复发等研究认为是由外周血中存在的循环肿瘤细胞所致（circulating tumor cell,CTC）。CTCs存在于外周循环中,激发机体的免疫反应,大部分肿瘤细胞被机体免疫系统所识别难以生存,只有小部分细胞继续在循环中,穿透基底膜,侵出血管在远端形成肿瘤转移灶。CTCs是肿瘤发生远处转移的必要条件,深入研究循环肿瘤细胞有助于对肿瘤的转移机制有更多的了解。本文对CTCs的分离与鉴定技术方法和CTCs与肿瘤复发转移的机制进行综述。     

肿瘤原发灶的治疗与其转移灶之间关系的研究进展

由肿瘤原发灶产生的一些因子，可通过循环血液到达肿瘤转移灶，对转移灶产生促进或抑制作用，肿瘤原发病灶的治疗有可能加速其转移灶的生长，本文就肿瘤原发灶的治疗与肿瘤转移灶的关系做了介绍。     

肿瘤原发灶的治疗与其转移灶之间关系的研究进展

由肿瘤原发灶产生的一些因子，可通过循环血液到达肿瘤转移灶，对转移灶产生促进或抑制作用。肿瘤原发病灶的治疗有可能加速其转移灶的生长。本文就肿瘤原发灶的治疗与肿瘤转移灶的关系做了介绍。     

循环肿瘤细胞的体外培养与应用

循环肿瘤细胞（circulating tumor cells, CTCs）是原发灶或转移灶中的癌细胞播散到循环系统所形成,在肿瘤早期诊断、转移复发监控、疗效评价中都有重要价值,尤其可成为转移干预的重要靶点。CTCs体外培养可为转移干预药物的筛选提供模型以及提高CTCs表型分析的精度。但目前CTCs的体外培养难度较大,成为制约该领域研究的瓶颈。未来本领域研究的首要任务是鉴别出真正导致转移的CTC亚群的分子特征,进而以之构建转移干预药物的体外筛选平台,从而提高转移干预的疗效。本文对CTCs的提取,培养方法,以及体外研究进展进行了系统综述,以期推动该领域的进展。     

转移性循环肿瘤细胞的特征

循环肿瘤细胞（circulating tumor cells，CTCs）是肿瘤转移的潜在种植者。这些引起肿瘤转移的CTCs具有干性、转化、簇群、亲器官性和变形等特征，最终在靶器官形成转移灶。研究CTCs的特征可能揭开肿瘤转移的机制。     

结直肠癌循环肿瘤细胞临床应用进展

结直肠癌是最常见的恶性肿瘤之一。在原发灶的早期阶段以及手术和化疗后,癌细胞可进入血液、形成远处转移灶,导致治疗效果差、预后不良。如果在转移灶形成之前能够在血液中发现循环肿瘤细胞(CTCs)则可早期发现转移倾向,同时为治疗期间监测治疗效果、判断预后提供有效数据,因而,能否有效地检测出结直肠癌CTCs直接关系到预后。目前开发更加特异、敏感的CTCs分子标记物以及更加高效的CTCs检测技术,对于提高结直肠癌CTCs的检出率具有重要的临床应用价值。本文就结直肠癌CTCs检测及临床应用做一综述。     

循环肿瘤细胞检测技术在胃癌诊治中应用的研究进展

胃癌是一种致死性很强的恶性肿瘤,在东亚地区尤其在中国是一个严重的公共卫生问题。循环肿瘤细胞（CTCs）被认为在癌症转移中起关键作用,是罕见的从肿瘤原发灶释放到血流的肿瘤细胞。循环肿瘤细胞也被认为是较好的肿瘤标志物,有助于提高诊断、评估预后及提高胃癌患者的治疗水平。本文对CTCs的检测技术及在胃癌临床应用的研究进展作一综述。     

肺癌循环肿瘤细胞的研究进展

转移和复发是肺癌患者死亡的主要原因。研究发现循环肿瘤细胞(circula tingtumo rcells,CTCs)在肺癌转移和复发中起着重要作用。而且随着靶向治疗的不断进步,对于晚期无法取得肺癌实体组织的患者,CTCs作为一种肺癌组织替代物可以决定治疗方案。所以CTCs在早期发现肺癌患者的微转移、检测肿瘤复发、评估预后和选择个体化治疗方案方面有着重要作用。本文针对CTCs的研究进展及肺癌领域的应用进行综述。     

乳酸脱氢酶A促进恶性肿瘤发生发展机制的研究进展

乳酸脱氢酶A(LDH-A)是肿瘤细胞有氧糖酵解过程中的关键酶，在肿瘤细胞的代谢改变中扮演着重要角色。研究发现，LDH-A在多种肿瘤中具有明显的高表达特性，能够促进肿瘤的进展和转移，同时它也是肿瘤治疗过程中极具希望的新靶点。其如何促进肿瘤的具体机制是目前的研究热点之一，本文着重对当前比较公认的几种机制作一综述。     

Chromogranin A regulates tumor self-seeding and dissemination

Cancer progression involves the seeding of malignant cells in circulation and the colonization of distant organs. However, circulating neoplastic cells can also reinfiltrate the tumor of origin. This process, called "tumor-self seeding," can select more aggressive cells that may contribute to cancer progression. Here, using mouse mammary adenocarcinoma models, we observed that both tumor self-seeding and organ colonization were inhibited by chromogranin A (CgA), a protein present in variable amounts in the blood of cancer patients. Mechanism studies showed that CgA inhibited the shedding of cancer cells in circulation from primary tumors, as well as the reinfiltration of tumors and the colonization of lungs by circulating tumor cells. CgA reduced gap formation induced by tumor cell-derived factors in endothelial cells, decreased vascular leakage in tumors, and inhibited the transendothelial migration of cancer cells. Together, our findings point to a role for circulating CgA in the regulation of tumor cell trafficking from tumor-to-blood and from blood-to-tumor/normal tissues. Inhibition of the multidirectional trafficking of cancer cells in normal and neoplastic tissues may represent a novel strategy to reduce cancer progression.     

循环肿瘤细胞自我种植对裸鼠骨肉瘤生长的促进作用

目的：通过建立骨肉瘤裸鼠荷瘤模型,观察骨肉瘤中是否存在循环肿瘤细胞自我种植现象,并探讨其在骨肉瘤进展中的作用。方法：建立骨肉瘤裸鼠原位荷瘤模型后,处理组尾静脉注射红色荧光蛋白（RFP）标记循环肿瘤细胞,对照组注射PBS,2周后将处理组原位瘤体冰冻切片荧光显微镜下观察有无自我种植,并根据肿瘤生长指标（大小、重量、生长曲线）将处理组与对照组进行比较分析。结果：处理组瘤体冰冻切片后荧光显微镜下观察发现,原位瘤组织中有红色荧光散在分布,即存在循环肿瘤细胞自我种植现象。肿瘤生长各指标比较发现,处理组瘤体在大小、重量、生长速率上均显著高于对照组（P〈0.05）,具有统计学意义。结论：骨肉瘤中存在循环肿瘤细胞自我种植现象,并且能够促进原位灶的生长。     

EMT,CTCs and CSCs in tumor relapse and drug-resistance

Tumor relapse and metastasis are the primary causes of poor survival rates in patients with advanced cancer despite successful resection or chemotherapeutic treatment. A primary cause of relapse and metastasis is the persistence of cancer stem cells (CSCs), which are highly resistant to chemotherapy. Although highly efficacious drugs suppressing several subpopulations of CSCs in various tissue-specific cancers are available, recurrence is still common in patients. To find more suitable therapy for relapse, the mechanisms underlying metastasis and drug-resistance associated with relapse-initiating CSCs need to be identified. Recent studies in circulating tumor cells (CTCs) of some cancer patients manifest phenotypes of both CSCs and epithelial-mesenchymal transition (EMT). These patients are unresponsive to standard chemotherapies and have low progression free survival, suggesting that EMT-positive CTCs are related to co-occur with or transform into relapse-initiating CSCs. Furthermore, EMT programming in cancer cells enables in the remodeling of extracellular matrix to break the dormancy of relapse-initiating CSCs. In this review, we extensively discuss the association of the EMT program with CTCs and CSCs to characterize a subpopulation of patients prone to relapses. Identifying the mechanisms by which EMT-transformed CTCs and CSCs initiate relapse could facilitate the development of new or enhanced personalized therapeutic regimens.     

循环肿瘤细胞自激注入的研究进展

由于缺乏有效的治疗手段,转移仍是癌症病人死亡的首要原因。肿瘤转移的新理论认为循环肿瘤细胞能够回到肿瘤原发灶,从而滋养肿瘤细胞,并产生更具侵袭力的转移株。本文就该现象加以综述,并对其在人类癌症转移研究中的意义进行探讨。     

循环肿瘤细胞自激注入的研究进展

由于缺乏有效的治疗手段,转移仍是癌症病人死亡的首要原因。肿瘤转移的新理论认为循环肿瘤细胞能够回到肿瘤原发灶,从而滋养肿瘤细胞,并产生更具侵袭力的转移株。本文就该现象加以综述,并对其在人类癌症转移研究中的意义进行探讨。     

Circulating tumor cells in pancreatic cancer patients: Methods of detection and clinical implications

The poor prognosis of pancreatic cancer patients is associated with the frequent and early dissemination of the disease, as well as late detection due to unspecific and late symptoms from the primary tumor. Pancreatic cancers frequently spread to the liver, lung and skeletal system, suggesting that pancreatic tumor cells must be able to intravasate and travel through the circulation to distant organs. Circulating tumor cells (CTCs) are tumor cells that have acquired the ability to enter the circulatory system; this cell population is ultimately responsible for the development of metastases in distant organs. Clinical studies have revealed that the presence of CTCs in blood is correlated with disease progression for other cancers, such as breast, colorectal and prostate cancer. However, as CTCs are extremely rare, both enrichment and sensitive methods of detection are required for their enumeration. This review highlights various enrichment procedures and methods for the detection of CTCs. Furthermore, we systematically review previously reported studies of the clinical relevance of CTC detection in pancreatic cancer patients. There is evidence that the presence of CTCs also correlates with an unfavorable outcome in pancreatic cancer patients. However, technical/methodological issues may explain why some studies only show a trend toward an association between CTC detection and disease progression. Larger studies, as well as characterization of the CTC population, are required to achieve further insight into the clinical implications of CTC detection in pancreatic cancer patients.